This project involves a multidisciplinary investigation of the pathogenesis and prevention of mineralocorticoid-induced hypertension in the rat. Methods are at present available for the measurement of 11- deoxycorticosterone (DOC) by radioimmunoassay and now we will prepare steroid-protein conjugates of 18-hydroxy-DOC and aldosterone. Using these conjugates, antibodies to 18-hydroxy-DOC and aldosterone will be raised and used in developing methodology for their assay in peripheral plasma. DOC, 18-hydroxy-DOC and aldosterone will be measured in various forms of experimental hypertension in order to determine the steroid profile contributing to the development of the hypertension. The adrenal mitochondrial cytochrome P-450 enzymes will be examined by EPR techniques to identify the defects in corticosteroidogenesis that may be present. We will also expand our studies on the prevention of hypertension by immunization against mineralocorticoids and thus follow up on our recent finding that adrenal regeneration hypertension can be controlled in this way. We will evaluate the potential of immunization against DOC and 18- hydroxy-DOC in androgen-induced hypertension, adrenal-regeneration hypertension, salt-susceptible hypertension of Dahl, spontaneous hypertension of Okamoto-Aoki rats and also immunization against aldosterone in renovascular hypertension. The success of the immunization procedures in reversing lesions in the cardiovascular system will be measured by quantitative electron microscopic stereology.